HK1170304A1

HK1170304A1 - Reaction cuvette

Info

Publication number: HK1170304A1
Application number: HK12110777.4A
Authority: HK
Inventors: Shintani Etsurou; Goukura Akira; Yokota Kenichi; Ogura Minoru
Original assignee: Phc Corporation
Priority date: 2005-04-01
Filing date: 2012-10-29
Publication date: 2013-02-22
Also published as: CN102565438A; CA2603209A1; JPWO2006107016A1; EP1870713A4; JP5364064B2; EP1870713B1; US9341640B2; KR20080005363A; KR101260400B1; JP4712033B2; JP2011017716A; CN101147071B; WO2006107016A1; EP1870713A1; ES2859774T3; CN102565438B; US20080318323A1; CN101147071A

Abstract

A biosample multiple autoanalyzer characterized by including: (1) a sample supply unit having a plurality of biosamples; (2) a first measuring unit fitted with a first optical measuring means capable of detachably holding, in a mutually independent fashion, a plurality of reaction cuvettes independent from each other; (3) a sample transport means capable of transporting the biosamples from the sample supply unit to the reaction cuvettes on the first measuring unit; (4) a second measuring unit fitted with a second optical measuring means capable of detachably holding, in a mutually independent fashion, a plurality of reaction cuvettes independent from each other; (5) a cuvette transfer means capable of transferring the reaction cuvettes on the first measuring unit to the second measuring unit; (6) a reagent supply unit having reagents for use in measuring by the first measuring unit and measuring by the second measuring unit; and (7) a reagent transport means capable of transporting reaction reagents, in a mutually independent fashion, from the reagent supply unit to the reaction cuvettes on the first measuring unit and/or second measuring unit, and characterized by being arranged such that the reaction cuvettes on the second measuring unit are dispensed with the biosamples on the first measuring unit, subsequently transferred from the first measuring unit to the second measuring unit by the cuvette transfer means, and retained thereon, and such that different measurements are carried out by the first measuring unit and the second measuring unit.

Description

Reaction cup

The present invention is a divisional application of an invention patent application named "apparatus and method for automatically analyzing biological samples and cuvettes" of PCT patent application PCT/JP2006/307040, application date 4/3/2006, and the application number of the parent application to china is 200680009807.5.

Technical Field

The present invention relates to a complex automatic analyzer, an automatic analyzing method, and a cuvette for biological samples.

Background

In the past, biochemical items such as enzymes have been the mainstream of automatic analyzers for measuring components in biological samples such as blood samples and urine samples. However, in recent years, there is a trend toward the measurement of immunological items such as hormones and tumor markers. In a biochemical automatic analyzer, a substance to be detected is generally measured by transmitted light or scattered light using a change in absorbance of a reaction solution caused by a biochemical reaction in a blood sample. In addition, some of the immunological items can be measured by such a biochemical automatic analyzer, and for example, some of the immunological items that do not require B/F separation and can be homogeneously measured can be measured by a change in absorbance by a latex agglutination method or the like.

On the other hand, in a serum immunoassay device used for an immunological item, a substance to be detected such as a hormone in a biological sample can be measured with high sensitivity by a heterogeneous assay in which an antibody or an antigen specifically binding to each substance to be detected prepared on the reagent side is labeled with a fluorescent dye or the like, and the labeled antibody or the labeled antigen obtained by labeling the antibody or the antigen is bound to the substance to be detected in the sample by an immunological reaction, and then B/F separation is performed to detect the labeled antibody or the labeled antigen.

However, with the recent increase in sensitivity of serum immunoassays, it is known that a case where a sample is present in a high concentration of a normal value or more and a case where the sample is present in an extremely small amount of a normal value or less in blood, such as thyroid stimulating hormone, show different pathological conditions. Therefore, when it is necessary to measure biochemical items and visually observe immunological items in the same sample, it has been conventionally necessary to measure the sample again by a biochemical automatic analyzer after the completion of the measurement by a serum immunoassay analyzer, or conversely, to measure the sample again by a serum immunoassay analyzer after the completion of the measurement by a biochemical automatic analyzer.

In this way, only the examination results obtained by 1 automatic analyzer are often insufficient for diagnosing the disease condition. For this reason, an analysis system configured to analyze a plurality of analysis items with one system has been proposed (for example, patent document 1). However, the configuration of this analysis system is such that a plurality of analysis units for biochemical analysis are arranged along the transport line of the rack, and is virtually indistinguishable from a configuration in which a plurality of automatic biochemical analyzers are simply juxtaposed.

In addition, a complex automatic analyzer in which a biochemical analysis unit and an immunoassay unit are integrated is also known (for example, patent document 2). However, in this apparatus, the biochemical analysis unit and the immunoassay unit are provided with a reagent supply unit and a device for performing reaction and measurement, respectively, and only the specimen rack for supplying the sample to the biochemical analysis unit and the immunoassay unit is moved along the specimen transport line and the sample is shared. The apparatus is also large, the space-saving effect is limited, and the effect of shortening the measurement and inspection time cannot be obtained.

Patent document 1: japanese laid-open patent publication No. 9-281113

Patent document 2: japanese patent laid-open No. 2001-4636

Disclosure of Invention

Accordingly, an object of the present invention is to provide an apparatus capable of measuring a plurality of types of analyses having different measurement accuracies, such as biochemical analysis and immunological analysis, by a single apparatus, and reducing the size of the apparatus and the measurement time by sharing components in the apparatus.

In addition, the present inventors have succeeded in developing a cuvette suitable for such an automatic analyzer in the course of the development of the above-mentioned apparatus.

The above object can be achieved by a combined automatic analyzer for biological samples according to the present invention, comprising:

(1) a sample supply unit having a plurality of biological samples,

(2) the 1 st measurement unit comprises a 1 st optical measurement device capable of detachably holding a plurality of cuvettes independent of each other,

(3) a sample transfer device for transferring a biological sample from the sample supply unit to the cuvette in the 1 st measurement unit,

(4) a 2 nd measurement unit having a 2 nd optical measurement device capable of detachably holding a plurality of cuvettes independent of each other,

(5) a cup transfer device for transferring the cuvette on the 1 st measuring unit to the 2 nd measuring unit,

(6) a reagent supply unit having a reagent used for the measurement in the first measurement unit and the measurement in the 2 nd measurement unit, and

(7) a reagent feeding device for feeding a reagent independently from each other from the reagent supply unit to the cuvette in the 1 st measurement unit and/or the 2 nd measurement unit,

the cuvette in the 2 nd measuring unit is transferred from the 1 st measuring unit to the 2 nd measuring unit by the cuvette transfer means after the biological sample is dispensed to the 1 st measuring unit and then held,

the measurement is performed by the 1 st measurement unit and the 2 nd measurement unit, which are different from each other.

In a preferred embodiment of the apparatus of the present invention, the measurement in the 1 st measurement unit and the measurement in the 2 nd measurement unit are measurements based on different measurement principles or different detection methods.

In a more preferred embodiment of the present invention, the 2 nd measuring unit performs measurement with higher accuracy than the 1 st measuring unit.

In another preferred embodiment of the present invention, the measurement in the 1 st measurement unit is a biochemical measurement or a latex agglutination measurement, and the measurement in the 2 nd measurement unit is an enzyme immunoassay.

In another preferred embodiment of the apparatus of the present invention, the 1 st measuring unit and the 2 nd measuring unit are rotatable disk-shaped, and have a placing region on a peripheral portion of the disk, the placing region being capable of transporting the cuvette in the direction of the rotational movement; or a plate type reciprocating motion having a loading area for transporting the reaction cup in the reciprocating direction.

In another preferred embodiment of the present invention, the apparatus further comprises 1 or more additional measuring units which are capable of detachably holding a plurality of cuvettes independently of each other, have an optical measuring device, and perform a measurement different from the measurement in the 1 st measuring unit and the measurement in the 2 nd measuring unit. In this embodiment, the cuvette in the additional measurement unit may be a disk type rotatable and may have a placement area on a peripheral edge of the disk, the placement area being capable of transporting the cuvette in the direction of the rotational movement; or a plate type reciprocating motion having a loading area for transporting the reaction cup in the reciprocating direction. In this embodiment, the measurement in the 1 st measuring unit may be a colorimetric or turbidimetric measurement, the measurement in the 2 nd measuring unit may be a chemiluminescence measurement, and the measurement in the additional measuring unit may be a blood coagulation time measurement.

In another preferred embodiment of the device of the present invention, the device further comprises 1 or more independent measuring units, the independent measuring units can directly supply the biological sample from the sample supply unit, and the measurement can be performed without supplying a reagent from the reagent supply unit. In this embodiment, the independent measurement unit is, for example, a body fluid electrolyte measurement unit.

In a more preferred embodiment of the device of the present invention, at least 1 of the measurement units has an abnormal sample detection device.

In another preferred embodiment of the apparatus of the present invention, the 1 st optical measurement device in the 1 st measurement unit, the 2 nd optical measurement device in the 2 nd measurement unit, and the optical measurement device in 1 or more than 1 additional measurement unit are respectively different optical detectors, and in this embodiment, the 1 st optical measurement device, the 2 nd optical measurement device, and the optical measurement device in 1 or more than 1 additional measurement unit are respectively different optical detectors, and they are, for example, any one of the following:

(1) optical detector comprising light emitting diodes and diode arrays

(2) An optical detection meter comprising a lamp unit and a beam splitter, and

(3) an optical detector includes a photomultiplier tube as a light receiver.

In another preferred embodiment of the apparatus of the present invention, the reagent supply unit has a plurality of concentric circular reagent storage lanes which are rotatable and stoppable independently in the same direction or in opposite directions, and each of the concentric circular reagent storage lanes stores a reagent to be supplied to each of the cuvettes carried by the 1 st measurement unit and the 2 nd measurement unit. In this embodiment, the reagent supply unit may further include a concentric circular reagent storage lane for storing a reagent to be supplied to 1 or more cuvettes supported by the additional measurement unit, and the reagent supply unit may further include a concentric circular reagent storage lane for storing a reagent to be supplied to 1 or more cuvettes supported by the independent measurement unit.

In another preferred embodiment of the apparatus of the present invention, the reaction cup is an arc-shaped reaction cup having a projection for placement provided so as to project from the upper side surface of the cup body. In this embodiment, the reaction cuvette may have a recess in the bottom surface of the cuvette body, the recess having a curved wall surface, and the reaction cuvette may have an insertion opening for the tip end of the stirring rod in the center of the recess. The reaction cup may have a fixing projection projecting downward from a lower surface of the placing projection.

The present invention also relates to a method for automatically analyzing a biological sample, which comprises using an analysis method comprising the following automatic analyzer,

(1) a sample supply unit having a plurality of biological samples,

(6) a reagent supply unit having a reagent used for the measurement in the 1 st measurement unit and the measurement in the 2 nd measurement unit, and

(7) a reagent feeding device for feeding a reagent independently from each other from the reagent supplying unit to the cuvettes in the 1 st measuring unit and/or the 2 nd measuring unit,

wherein the cuvette in the 2 nd measuring unit is moved from the 1 st measuring unit to the 2 nd measuring unit by the cuvette transfer means after the biological sample is dispensed to the 1 st measuring unit and is held,

the 1 st measuring unit and the 2 nd measuring unit are subjected to different measurements.

Further, the present invention relates to a reaction cup, wherein the placing projection provided to project from the upper side surface of the cup body is formed in an arc shape.

In a preferred embodiment of the reaction cuvette of the present invention, a concave portion having a curved wall surface is provided on the bottom surface of the cuvette body.

In a more preferred embodiment of the reaction cuvette of the present invention, an insertion opening for a distal end portion of the stirring rod is provided in a central portion of the well.

In a more preferred embodiment of the reaction cuvette of the present invention, the lower surface of the placement projection has a fixing projection piece projecting downward from the lower surface.

In the present specification, the terms "upper", "lower", "upper" and "lower" and the like indicating the vertical relationship in the automatic analyzer indicate the vertical relationship in a state where the automatic analysis is performed by the automatic analyzer, and do not specify the positional relationship in other states (for example, a state at the time of transportation and a state at the time of assembly). The same applies to the analytical method. Further, the terms "upper", "lower", "upper" and "lower" as used herein with respect to the cuvette also indicate the vertical relationship when the cuvette is used in an automatic analyzer and subjected to automatic analysis, and do not specify the positional relationship in a state other than that (for example, a state before and after mounting).

Effects of the invention

Since the automatic analyzer of the present invention has a plurality of measurement units, a plurality of kinds of analyses having different measurement accuracies, such as biochemical analysis and immunological analysis, can be measured by a single analyzer, and the measurement time can be shortened. Furthermore, the components in the device are shared, so that the device is small in scale and can save space.

Further, since the reaction cup of the present invention has the arc-shaped projection for placement, the stirring operation on the reaction base of each measurement unit can be smoothly performed.

Drawings

Fig. 1 is a plan view schematically showing the arrangement of each unit constituting the automatic compound analyzer according to the present invention.

FIG. 2 is an explanatory view schematically showing the measurement procedure in the 1 st measurement unit.

FIG. 3 is an explanatory view schematically showing the measurement procedure in the 2 nd measurement unit.

Fig. 4 is an explanatory view schematically showing the measurement procedure in the 3 rd measurement unit and the 4 th measurement unit.

FIG. 5 is a perspective view of a reaction cuvette according to the present invention.

FIG. 6 is a cross-sectional view of the reaction cup of FIG. 5.

FIG. 7 is a schematic cross-sectional view of the reaction cuvette of FIG. 5 mounted on a reaction base.

FIG. 8 is a schematic cross-sectional view showing a state where the cuvette shown in FIG. 5 is placed on a reaction base and stirring processing is started.

FIG. 9 is a perspective view of a cuvette having a fixing projection.

FIG. 10 is a cross-sectional view of the reaction cup of FIG. 9.

FIG. 11 is a partial sectional view of another embodiment of a reaction cup having a fixing projection.

Description of the symbols

1 … sample supply unit; 2 … measurement unit 1;

3 … measurement unit 2; 4 … reagent supply Unit

5 … measurement unit 3; 5a … transfer position

5b … additional reagent dispensing position; 5c … optical determination of position;

6 … th measurement unit 4;

7 … outer shell; 8 … reaction cup;

10 … complex automatic analysis device; 11 … sample collection location;

21 … reaction base station; 22 … reaction cup loading area;

25 … reaction cup; 25a … sample dispensing position;

25b … R1 reagent dispensing position; 25c … stir position;

25d … R2 reagent dispensing position; 25e … optically determining position;

25f … waste position; 25s, 25t … cup transfer position;

26 … optical measurement device; 31 … reaction base station;

a 32 … cuvette holding area;

35a … receiving position; 35b … R3 reagent dispensing position;

35c … stir position; 35d … B/F separation position;

a 35e … wash position; 35f … pick-up position;

37 … optical measurement device; 41 … reagent storage base station;

42a, 42b, 42c … reagent storage lane;

43 … reagent cup; 55a … receiving position;

55b … additional reagent dispensing position; 55c … optically determining position;

57 … optical measurement device; 81 … cup body;

82 … cup body upper end; 83 … a pick-up projection;

84 … placing the projection piece; 85 … bottom surface of the cup body;

86 … hemispherical dimples; 87 … inserting the tip end of the stirring rod into the opening;

88 … fixing tab; 91 … stirring rod.

Detailed Description

Representative embodiments of the complex automatic analyzer of the present invention are described with reference to the accompanying drawings.

Fig. 1 is a schematic plan view showing the arrangement of each unit constituting the automatic compound analyzer 10 of the present invention. As shown in fig. 1, the complex automatic analyzer 10 of the present invention includes a sample supply unit 1, a 1 st measurement unit 2, a 2 nd measurement unit 3, and a reagent supply unit 4 in a casing 7, may further include a 3 rd measurement unit 5 as an additional measurement unit, and may further include a 4 th measurement unit 6 as a stand-alone measurement unit.

The sample supply unit 1 has a sample holder that detachably holds a plurality of sample cups filled with a biological sample (for example, a blood sample or a urine sample). The sample supply unit 1 transports a predetermined sample cup to the sample collection position 11 by moving in the direction of arrow a and/or arrow B in fig. 1, and at the sample collection position 11, a predetermined biological sample is dispensed into a cuvette held by the measurement unit 1 at the measurement unit 2 by a sample dispensing pipette (not shown). The sample dispensing pipette may be, for example, a suspension type pipette which is suspended from the top plate portion of the housing 7 and is movable along a guide rail provided in the top plate portion, and may be moved to a position above a predetermined sample cup in the sample supply unit 1 without moving the sample supply unit 1, collect a biological sample, then move to a position above a reaction cup held in the 1 st measurement unit 2, and dispense the biological sample into the reaction cup. In this case, the sample supply unit 1 can be fixedly disposed at a predetermined position in the housing 7, and it is not necessary to provide a moving device for the sample supply unit 1.

The 1 st measurement unit 2 typically includes a turntable-type (disk-type) reaction base 21, and an annular reaction cup placement area 22 is provided along the circumference of the reaction base 21. The reaction base 21 is rotatable in a clockwise direction or a counterclockwise direction (the direction of arrow D) and can be stopped at a predetermined position (for example, a sample/reagent dispensing position, a stirring position, a measurement position, a disposal position, etc.). The cuvette holding section 22 can hold a plurality of cuvettes 25 independently and detachably. In the cuvette holding section 22, the plurality of cuvettes 25 are arranged in a row in the circumferential direction, and there is almost no gap between the adjacent cuvettes, but in fig. 1, the cuvettes 25 are shown with a gap therebetween.

The 2 nd measurement unit 3 typically also includes a turntable-type (disk-type) reaction base 31, and an annular reaction cup placement area 32 is provided along the circumference of the reaction base 31. The reaction base 31 can also rotate clockwise or counterclockwise (in the direction of the arrow F) and can be stopped at a predetermined position (for example, a reagent dispensing position, a stirring position, a measurement position, a disposal position, etc.). The rotational movement and stopping of the 2 nd measuring unit 3 may be synchronized with the rotational movement and stopping of the 1 st measuring unit 2, or may be performed independently of each other. The cuvette holding section 32 can hold a plurality of cuvettes 25 independently and detachably. In the cuvette holding section 32, the plurality of cuvettes 25 are arranged in a row in the circumferential direction, and there is almost no gap between the adjacent cuvettes, but in fig. 1, these cuvettes 25 are shown with a gap therebetween.

The reagent supply unit 4 typically includes a rotary table-type (disk-type) reagent storage base 41, and a plurality of concentric circular annular reagent storage paths 42a, 42b, and 42c are provided on the reagent storage base 41. In each of the reagent storage paths 42a, 42b, and 42c, a reagent cup 43 is stored which stores various reagents necessary for measurement in each measurement unit (for example, the 1 st measurement unit 2, the 2 nd measurement unit 3, or the 3 rd measurement unit 5 which is an additional unit) of the composite automatic analyzer of the present invention. The reagent storage base 41 is rotatable in a clockwise direction or a counterclockwise direction (the direction of the arrow K) and can be stopped at a predetermined position (for example, a reagent collection position, a reagent cup attachment/detachment position, etc.). In the reagent holding paths 42a, 42b, and 42c, the plurality of reagent cups 43 are arranged in 1 row along the circumferential direction, and there is almost no gap between adjacent reagent cups, but these reagent cups are shown with a gap therebetween in fig. 1. The number of the concentric circular reagent storage lanes is not limited to 3, and 2 or less or 4 or more reagent storage lanes may be provided.

The rotary table type reagent storage base 41 may have a structure in which the entire reagent storage base is rotatable as 1 disk, or may have a multiple ring structure in which a plurality of concentric circular reagent storage tracks (for example, the reagent storage tracks 42a, 42b, and 42c) are rotatable independently of one another. When the plurality of concentric circular reagent storage wells have a multi-ring structure capable of rotating independently of each other, the respective rings can be stopped independently of each other while performing circular motion or half-circular rotation independently of each other, and reagents can be supplied to the respective measurement units independently of each other and efficiently.

Next, the case of performing biochemical item measurement or latex aggregation measurement by a colorimetric or turbidimetric method in the 1 st measurement unit 2 will be described with reference to FIG. 2.

The empty cuvettes 25 placed in the cuvette placing areas 22 of the reaction base 21 of the 1 st measurement unit 2 are stopped at the sample distribution positions 25a, and supplied with the biological sample in the predetermined cuvettes 11 of the sample supply unit 1 by sample distribution pipettes (not shown) (see arrows C in fig. 1 and 2). Subsequently, the cuvette 25 is moved to the R1 reagent dispensing position 25b by the rotation of the reaction base 21 and stopped, and the R1 reagent is dispensed by the reagent supply unit 4 (see arrow L in fig. 2). The R1 reagent dispensing is performed by, for example, a suspension type reagent dispensing pipette (not shown) suspended from the top plate portion of the housing 7 and movable along a guide rail provided in the top plate portion. The suspension type reagent dispensing pipette is moved to a position above a predetermined reagent cup 43a of the reagent storage path 42a of the reagent supply unit 4, for example, to collect the R1 reagent, and then moved to a position above the cuvette 25 held at the R1 reagent dispensing position 25b of the 1 st measurement unit 2, and dispensed into the cuvette 25.

The cuvette 25 having the biological sample and the R1 reagent dispensed in this manner is moved to the stirring position 25c by the rotation of the reaction base 21 and stopped, and is subjected to the stirring operation. Subsequently, the reagent supply unit 4 dispenses the R2 reagent by moving the reaction base 21 to the R2 reagent dispensing position 25d and stopping the movement (see arrow M in fig. 2). The R2 reagent dispensing can also be performed by a suspension type reagent dispensing pipette (not shown) similar to the above. The suspension type reagent dispensing pipette is moved to a position above a predetermined reagent cup 43b of the reagent storage path 42b of the reagent supply unit 4, for example, to collect the R2 reagent, and then moved to a position above the cuvette 25 held at the R2 reagent dispensing position 25d of the 1 st measurement unit 2, and dispensed into the cuvette 25.

The cuvette 25 having the biological sample, the R1 reagent, and the R2 reagent dispensed in this manner is moved to the stirring position 25c by the rotation of the reaction base 21 and stopped, and is subjected to the stirring operation. The stirring position for the 2 nd stirring may be other positions. Then, the reaction base 21 is rotated to pass through the optical measurement position 25e, and during the passage, the change caused by the reaction in the cuvette is measured by the optical measurement device 26 which can measure the change by transmitted light, scattered light, or the like. When the above optical measurement is performed, the cuvette 25 may be stopped at the optical measurement position 25 e. Then, the cuvette 25 is finally moved to the disposal position 25f and stopped, taken out from the reaction base 21 by a pickup device (not shown), and disposed of in a disposal chamber (not shown).

Next, the case of performing an enzyme immunoassay using chemiluminescence in the 2 nd measurement unit 3 will be described with reference to FIG. 3.

When the measurement in the 2 nd measurement unit 3 is performed, the sample distribution and a part of the reagent distribution (or only the sample distribution) are also performed on the reaction base 21 of the 1 st measurement unit 2. That is, first, the empty cuvettes 25 placed in the cuvette placing areas 22 of the reaction base 21 of the 1 st measurement unit 2 are stopped at the sample distribution positions 25a, and the biological sample in the predetermined cuvettes 11 of the sample supply unit 1 is supplied to the cuvettes 25 by the sample distribution pipettes (not shown) in the same manner as described above (see arrow C in fig. 3). Subsequently, the cuvette 25 is moved to the R1 reagent dispensing position 25b by the rotation of the reaction base 21 and stopped, and the R1 reagent is dispensed from the reagent supply unit 4 by, for example, a suspension type reagent dispensing pipette (not shown) (see arrow L in fig. 3).

The cuvette 25 into which the biological sample and the R1 reagent are dispensed is moved to the stirring position 25c and stopped, and is subjected to the stirring operation, as described above. Subsequently, the reagent supply unit 4 moves to the R2 reagent dispensing position 25d and stops dispensing the R2 reagent (see arrow M in fig. 3). Subsequently, after the stirring operation is received at the stirring position 25c as necessary, the reaction cup 25 is moved to the cup transfer position 25t and stopped.

The cuvette 25 is taken out from the reaction base 21 at the cup moving position 25t by a pickup device (not shown), transferred to the reaction base 31 of the 2 nd measurement unit 3 (see arrow E), and moved to the receiving position 35 a. Subsequently, the cuvette 25 is moved to the R3 reagent dispensing position 35b and stopped as necessary by the rotation of the reaction base 31 (see arrow F), and the R3 reagent is dispensed from the reagent supply unit 4 (see arrow N in fig. 3). The R3 reagent dispensing may be performed, for example, by a suspension-type reagent dispensing pipette (not shown). The suspension type reagent dispensing pipette is moved to a position above a predetermined reagent cup 43c of the reagent storage path 42c of the reagent supply unit 4, for example, to collect the R3 reagent, and then moved to a position above the cuvette 25 held at the R3 reagent dispensing position 35b of the 2 nd measurement unit 3, and dispensed into the cuvette 25. Note that this step may be omitted when the R3 reagent does not need to be dispensed. In addition, the R2 reagent may not be dispensed in the 1 st measurement cell 2, and the R2 reagent may be dispensed at the R3 reagent dispensing position 35 b.

The cuvette 25 having the R3 reagent (or the R2 reagent) dispensed in this manner moves to the stirring position 35c by the rotation of the reaction base 31 and stops, and is subjected to the stirring operation. Next, the reaction cuvette 25 is subjected to a B/F separation operation at the B/F separation position 35 d. In this case, the B/F separation operation can be performed by a magnet when using magnetic beads. When a magnet is used, it takes a relatively long time to collect the magnetic beads, and therefore the reaction base 31 is stopped for a relatively long time. However, in the apparatus of the present invention, since the reaction base 31 of the 2 nd measurement unit 3 is separated from the reaction base 21 of the 1 st measurement unit 2, the long stop time of the rotational movement can prevent the whole processing time from becoming long.

After the B/F separation operation is performed, the cuvette 25 is moved to the washing position 35e and stopped, and is subjected to a washing operation. Then, the optical measurement apparatus 33 is moved to the pickup position 35f and stopped, and is transferred to the optical measurement apparatus 33 by an appropriate pickup device (not shown). The optical measurement device 33 is a device that can measure a change caused by a reaction in a cuvette by chemiluminescence, for example. The optical measurement may be performed on the reaction base 31. When the above-mentioned optical measurement is performed on the reaction base 31, the measurement may be performed while the cuvette 25 passes through an optical measurement position (not shown), or the measurement may be performed while the cuvette 25 is stopped at the optical measurement position (not shown). After the measurement, the optical measurement device 33 is taken out and discarded in a disposal chamber (not shown).

The complex automatic analyzer of the present invention may further include 1 or more additional measuring units in addition to the 1 st measuring unit 2 and the 2 nd measuring unit 3.

The additional measurement unit may be a cuvette type (pre-supply type) in which the biological sample is distributed to the 1 st measurement unit 1 and a part of the reagent is further distributed according to circumstances, which is received from the 1 st measurement unit 1 by an appropriate cup transfer device, or a cuvette type (direct supply type) in which the biological sample is directly supplied from the sample supply unit 1. The additional measurement unit may be an additional reagent replenishment type requiring the additional reagent to be supplied from the reagent supply unit 4, or an unnecessary additional reagent type requiring no additional reagent to be supplied from the reagent supply unit 4.

The complex automatic analyzer of the present invention may have 1 or more independent measuring units in addition to the 1 st measuring unit 2 and the 2 nd measuring unit 3, or in addition to or instead of the additional measuring unit. The independent measuring unit can supply a biological sample directly from the sample supply unit 1, and can perform measurement without supplying a reagent from the reagent supply unit 4. The independent measurement unit is, for example, a body fluid electrolyte measurement unit.

The embodiment including the 3 rd measuring unit 5 of the pre-supply type and the additional reagent-replenishment type as the additional measuring unit and the 4 th measuring unit 6 as the independent measuring unit will be described with reference to fig. 4. In the pre-supply type and additional reagent-replenishment type 3 rd measurement unit 5, for example, blood coagulation time measurement can be performed, which is different from the measurement in the 1 st measurement unit 2 and the 2 nd measurement unit 3. When the measurement is performed in the 3 rd measurement unit 5 of the pre-supply type, the sample distribution and a part of the reagent distribution are performed on the reaction base 21 of the 1 st measurement unit 2. That is, first, the empty cuvette 25 placed on the cuvette placing section 22 of the reaction base 21 of the measurement unit 1 is stopped at the sample distribution position 25a, and the biological sample is supplied from the sample supply unit 1 to the cuvette 25 by the sample distribution pipette (not shown) in the same manner as described above (see arrow C in fig. 4). Subsequently, the cuvette 25 is moved to the R1 reagent dispensing position 25b and stopped, and the R1 reagent is dispensed from the reagent supply unit 4 by, for example, a suspension type reagent dispensing pipette (not shown). In the 1 st measurement unit 2, only sample dispensing may be performed, and reagent dispensing may not be performed.

Subsequently, the same stirring operation and R2 reagent dispensing operation as described above are performed as necessary, and then the cuvette 25 is moved to the cuvette transfer position 25s and stopped. The cup is taken out of the reaction base 21 at the cup transfer position 25s by a pickup device (not shown) and transferred to a receiving position 55a (see an arrow G) of the reaction base 51 of the 3 rd measurement unit 5 located at the transfer position 5a (indicated by a broken line in fig. 4). The 3 rd measuring unit 5 may be of a type including a circular rotary table type reaction base, or a type including a belt-shaped table type reaction base which is linearly reciprocated (in the direction of the arrow H and in the opposite direction) as in the 1 st measuring unit 2 and the 2 nd measuring unit 3.

The 3 rd measurement unit 5 having received the cuvette 25 at the transfer position 5a is moved to and stopped at an additional reagent dispensing position 5b (indicated by a solid line in fig. 4) by linear sliding (in the direction of arrow H) of the reaction base 51, and the additional reagent is dispensed from the reagent supply unit 4 at the additional reagent dispensing position 55b by, for example, a suspension type reagent dispensing pipette (not shown) (see arrow P). Further, an optical measurement device (not shown) is provided on the reaction base 51 at a position where the cuvette 25 is placed. For example, since optical measurement devices including a transmission light measurement signal emitting unit and a transmission light measurement signal receiving unit are provided on both sides of the position where the cuvette 25 is placed, transmission light measurement can be performed at intervals of, for example, 0.1 second. Note that, instead of providing an optical measurement device on the reaction base 51, for example, as shown in fig. 4, the optical measurement device may be moved to an optical measurement position 5c (indicated by a broken line in fig. 4) by linear sliding (in the direction of an arrow H) of the reaction base 51 and stopped, and the change caused by the reaction in the cuvette may be measured at the optical measurement position 5c by, for example, an optical measurement device 57 that can measure the change by scattered light. After the measurement, the reaction chamber is moved to a disposal position (not shown), stopped, taken out from the reaction base 51 by a pickup device (not shown), and disposed of in a disposal chamber (not shown).

The biological sample is directly supplied from the sample supply means 1 to the 4 th measurement means 6 (see arrow J in fig. 4) which is a stand-alone measurement means by a sample dispensing pipette (not shown). The 4 th measuring unit 6 may be, for example, a body fluid electrolyte measuring unit, particularly an ion detecting device having various ion selective electrodes. Examples of the ion-selective electrode include a halogen ion-selective electrode and an alkali metal ion-selective electrode.

In the automatic analyzer of the present invention, the 1 st measuring unit, the 2 nd measuring unit, and optionally 1 or more additional measuring units are provided, except that the sample is commonly supplied to the 1 st measuring unit by the sample supplying unit, and the installation position, the installation order (adjacent relationship), the type of the measurement item of each measuring unit, and the type of the optical measuring device installed in each measuring unit are not particularly limited.

In the automated multiplex analyzer according to the present invention, the sample supply means dispenses the sample to the plurality of cuvettes independently of each other in a batch manner in the 1 st measurement means, and therefore, the sample supply means and the 1 st measurement means are preferably disposed at adjacent positions. If the sample supply unit and the 1 st measuring unit are in close proximity, the movement of the sample transport device for dispensing is simple and short, the dispensing operation time can be shortened, and the device structure can be simplified. That is, in the multiple automatic analyzer of the present invention, as compared with the conventional apparatus in which samples are individually distributed to each measurement unit, the distribution of samples is performed in a batch in the 1 st measurement unit, and only the cuvettes are moved to the 2 nd measurement unit and the additional measurement unit (e.g., the 3 rd measurement unit) by the cup transfer device, the entire processing time including the sample distribution time is shortened, and the structure can be simplified.

For example, the 1 st measurement unit may be used for biochemical measurement or immunological measurement. Examples of the biochemical measurement target include targets to be used in ordinary biochemical clinical tests, such as various enzymes, carbohydrates, lipids, plasma (serum) proteins, nonprotein nitrogen compounds, biochrome, and tumor markers. Examples of the immunological measurement include immunological measurement using transmitted light or scattered light, such as immunoturbidimetry and latex agglutination, and examples of the target of measurement include D-dimer, FDP, and HCV.

The measurement unit 2 can perform a reaction system different from that of other measurement units, for example, measurement with high accuracy. As a highly sensitive measurement, a reaction of a specific affinity substance can be particularly utilized. Examples of the reaction of the specific affinity substance include an antigen-antibody reaction, a complementary base reaction of a nucleic acid (DNA or RNA), or a reaction of a receptor and a ligand thereof.

In the reaction of the specific affinity substance, the amount of the substance bound to the specific affinity substance is measured. In this case, the method is roughly classified into a homogeneous measurement method (homogeneous measurement method) in which the specific affinity substance and the analyte are bound to each other and the nature of itself or the tracer bound thereto is changed, and a heterogeneous method (heterogeneous method) in which a B/F separation operation is required to separate the bound substance and the unbound substance bound to the specific affinity substance after the complex of the specific affinity substance and the analyte is rendered insoluble. In the present invention, any of the homogeneous method and the heterogeneous method can be carried out in the above-mentioned 2 nd measurement unit. In addition, as the tracer, any of a method using a radioisotope and an enzyme immunoassay method (EIA) using an enzyme can be used.

The measurement unit 2 may be, for example, FIA, EIA or CLEIA. Examples of the target substance to be measured include CEA, CA 19-9, T3, T4, FT3, FT4, HBsAg, TAT, and TSH.

In the 3 rd measuring unit, for example, blood coagulation time measurement or activity measurement using a synthetic substrate can be performed. Examples of the measurement of the blood coagulation time include プロトビン time, activated partial thromboplastin time, and fibrinogen measurement. Examples of the activity assay using the synthetic matrix include assays for plasminogen, plasmin inhibitor, and antithrombin. In the above-mentioned 4 th measurement unit, for example, electrolyte measurement can be performed. Examples of the object of the electrolyte measurement include Na ion, K ion, and chloride ion.

In the 1 st measurement unit, measurement using transmitted light or scattered light, for example, colorimetry or turbidimetry is preferably performed. In the 2 nd measurement unit, measurement using chemiluminescence or fluorescence, for example, CLEIA is preferably performed. In the 3 rd measuring unit, measurement using transmitted light or scattered light, for example, a blood coagulation time measuring method is preferably performed. In the 4 th measurement unit, measurement using an electromotive force, for example, an ion selective electrode method is preferably performed.

In the composite automatic analyzer of the present invention, a preferable combination is: in the 1 st measuring unit, biochemical measurement or latex aggregation measurement is performed by a colorimetric or turbidimetric method, in the 2 nd measuring unit, enzymatic immunological measurement is performed by chemiluminescence, and in the 3 rd measuring unit, blood coagulation time measurement is performed. Further, in addition to the above combination, ion analysis is preferably performed in the 4 th measurement cell. It is more preferable that the chemiluminescence enzyme immunoassay in the aforementioned unit for measurement 2 is carried out using a magnetic carrier. In this case, the B/F separation may be performed by using a magnet as a known technique.

In the composite automatic analyzer of the present invention, the 1 st optical measuring device in the 1 st measuring unit, the 2 nd optical measuring device in the 2 nd measuring unit, and the 3 rd optical measuring device in the 3 rd measuring unit as the additional measuring unit are preferably different optical detectors from each other. As the 1 st optical measurement device, the 2 nd optical measurement device, and the 3 rd optical measurement device, for example:

(1) optical detector comprising light emitting diodes and diode arrays

(2) An optical detection meter comprising a lamp unit and a beam splitter, and

(3) an optical detector including a photomultiplier as a light receiver.

An optical detector including a light emitting diode and a diode array can be used for measurement of blood coagulation time, for example, an optical detector including a lamp unit and a spectroscope can be used for colorimetric measurement and turbidity measurement, and an optical detector including a photomultiplier as a light receiver can be used for measurement of chemiluminescence, for example.

In the automatic analyzer of the present invention, it is preferable that each measurement cell or any one of the measurement cells is provided with a device for detecting an abnormal sample. The abnormal sample is a sample in which the concentration of the test object substance is extremely high, and the high concentration cannot be detected in many cases. The abnormal sample also includes a non-specific sample (a sample in which magnetic latex is aggregated). Such abnormal samples can be detected, for example, by a change in absorbance.

The invention also relates to a reaction cup.

Exemplary embodiments of the reaction cup of the present invention are described with reference to FIGS. 5 to 8.

FIG. 5 is a perspective view of a reaction cup 8 of the present invention, and FIG. 6 is a sectional view thereof. Fig. 7 is a schematic cross-sectional view of the complex automatic analyzer shown in fig. 1 to 4, which is mounted on the reaction base 21 of the measurement unit 2 of the 1 st position, and fig. 8 is a schematic cross-sectional view showing a state in which the cuvette is tilted by the stirring rod.

The reaction cuvette 8 of the present invention has a pair of picking-up projections 83, 83 at an upper end 82 of a substantially quadrangular prism-shaped cuvette body 81, and further has a pair of placing projections 84, 84 at a lower part thereof. The cuvette 8 can be placed by inserting the lower portion of the cup body 81 into a through-hole for placement (or a well or a groove for placement) provided in the reaction base of the measurement unit. For example, in the case where the cuvette placed on the reaction base 21 of the 1 st measurement unit 2 is picked up and transferred to the reaction base 31 of the 2 nd measurement unit 3 or the like in the automatic analyzer shown in fig. 1 to 4, the pickup projection piece 83 is used as a member for holding the pickup device. Therefore, when the cuvette 8 is placed on the reaction base of the measurement unit, the pick-up projection piece 83 must be provided at a position that extends upward from the surface of the reaction base of the measurement unit so that the pick-up device can hold the pick-up projection piece 83.

The placing projection piece 84 is provided at an upper portion of the cup body 81, and for example, in the multiple automatic analyzer shown in fig. 1 to 4, when the cuvette is inserted into a placing through-hole (or a placing recess or groove) provided in the reaction base 21 of the 1 st measurement unit 2 (or the reaction base 31 of the 2 nd measurement unit 3) and placed, it functions as a fixing member which is brought into contact with the base surface of the reaction base 21 (or the reaction base 31) and does not fall down. In the reaction cuvette 8 of the present invention, a hemispherical recess 86 is provided in a bottom surface 85 of the cuvette body 81, and an insertion port 87 into which a tip end of the stirring rod 91 can be inserted is provided in a center portion of the recess 86.

As shown in fig. 7 and 8, the reaction cuvette 8 of the present invention having such a configuration is inserted into the through-hole for placement of the reaction base 21, moved to the stirring operation position and stopped, and then the tip of the stirring rod 91 of the stirring device (not shown) is inserted into the hemispherical recess 86. At this time, as shown in FIG. 7, the tip end of the stirring rod 91 is deviated from the midpoint in the circumferential direction and is not inserted into the center of the bottom 85 of the reaction cup 8. Since the tip of the stirring rod 91 inserted into the hemispherical recess 86 in a biased manner abuts against the wall surface of the hemispherical recess 86, the reaction cup 8 is tilted on the reaction base 21 as shown in fig. 8. However, when the tip end of the stirring rod 91 is further pressed upward against the hemispherical recess 86, it is finally inserted into the insertion port 87.

In the reaction cup 8 of the present invention, the tip of the stirring rod 91 is curved so that contact with the surface of the reaction base 21 is not irregular when the tip of the stirring rod 91 is brought into contact with the wall surface of the hemispherical recess 86 to stir the reaction cup 8, and in this case, if the placing projection piece 84 is formed in a square plate shape, contact with the surface of the reaction base 21 becomes irregular, and the reaction cup 8 is stirred smoothly. Therefore, the reaction cuvette of the present invention can be effectively used in an automatic analyzer for performing a stirring operation.

The concave pit provided on the bottom surface of the reaction cup of the present invention has a curved wall surface. The curved wall surface is preferably in a form such that the tip end portion of the stirring rod, which is initially in contact with the wall surface at the peripheral portion of the well, is smoothly guided into the central portion of the well finally during the stirring operation. Therefore, the curved wall surface may be, for example, a hemispherical shape, a semi-ellipsoidal shape, a conical shape, or a truncated conical shape as shown in fig. 6 to 8. When the curved wall surface is hemispherical or semi-ellipsoidal, it is preferable that an insertion opening for the tip of the stirring rod is provided in the center of the depression. When the curved wall surface is a truncated cone, it is preferable that an insertion opening for the tip end portion of the stirring rod is provided in the center truncated portion. In addition, when the curved wall surface is conical, the conical apex can function as an insertion opening for the tip end of the stirring rod.

The reaction cuvette of the present invention can stir a sample by the action from the outside without inserting a stirring rod into the sample when stirring the sample, and is therefore advantageous, for example, when the measurement item includes a coagulation time measurement. When the solidification time is measured, if a stirring rod is inserted into a sample to stir, a solidification system is influenced, and the measurement result is incorrect.

The reaction cuvette of the present invention is preferably a cuvette body having 4 side surfaces in a substantially quadrangular prism shape which are parallel flat surfaces so as to be advantageous for measurement by transmitted light, for example, turbidity measurement in biochemical measurement items and LPIA. Further, the reaction cuvette of the present invention preferably has a curved portion (a semi-spherical bottom portion or a semi-ellipsoidal bottom portion) at the inner bottom portion. If the inner bottom portion has no bent portion, the liquid may migrate upward along the inner wall of the cup due to capillary action, resulting in insufficient washing, and in particular, in the measurement of highly sensitive chemiluminescence, for example, an alkaline phosphatase-labeled antibody may remain, causing an error.

As shown in FIGS. 9 and 10, the reaction cuvette of the present invention may have fixing projections 88, 88 on the lower surface of one or both of the pair of placement projections 84, 84. The fixing projection piece 88 is a plate-like projection projecting downward from the lower surface of the placing projection piece 84, and a curved surface as shown in fig. 11 (partial sectional view) can be formed at the outer distal end portion on the side opposite to the cup main body side. When the reaction cuvette having the fixing projections is used, a recess or a groove is formed in the edge of the through-hole for mounting on the surface of the reaction base on which the reaction cuvette is mounted, the fixing projections 88 are inserted into the recess or the groove, and the lower portion of the cuvette body 81 is inserted into the through-hole for mounting. In this way, the fixing projections 88 are provided on the lower surface of one or both of the placing projections 84, 84 of the reaction cuvette, and the recesses or grooves for the fixing projections 88 are provided on the base surface of the reaction base, whereby the fixing and positioning of the cuvette can be reliably performed.

Preferred embodiments of the device according to the invention are summarized below.

In a preferred embodiment of the device of the invention, there are at least 3 different detection systems. As described above, the optical systems of the 1 st, 2 nd and 3 rd measuring units are different from each other. For example,

(1) using cells transmitting light, scattering light (detector comprising lamp unit and beam splitter)

(2) High sensitivity detecting unit (detecting device with photo-receiver including photomultiplier tube in chemiluminescence)

(3) A detection unit for the coagulation time (detection means comprising an array of LEDs and diodes),

all consisting of different detection systems.

To achieve this, it is necessary to have a mechanism for mounting each individual cup. Many conventional automatic analyzers have the following structure: the reaction cups are mechanically arranged in a connected state, and after reaction and detection are finished, reaction liquid is sucked and washed by washing liquid for reuse. In contrast, in the apparatus of the present invention, when "immunoturbidimetry", "chemiluminescence", and "coagulation time" are applied to the specimen a, and "chemiluminescence" and "coagulation time" are applied to the specimen B, samples are distributed to 3 cups for the specimen a and 2 cups for the specimen B at positions on a specific measurement unit. In each detection system, a cup necessary for stirring is stirred at a specific position, picked up (not shown, but the cup is lifted by an arm of the apparatus and mounted in a cup hole at a specific arrangement position of the next step), and transferred to each measurement unit, whereby each detection is performed independently and in parallel, and effective measurement can be performed.

In the apparatus of the present invention, the setting of a new cup in a specific apparatus of a specific measuring unit is also continuously and automatically performed. Of course, the reagent added to each cup in each measurement unit has a different composition (content) depending on the measurement system. In order to efficiently dispose a plurality of types of reagents, the reagent table area is one, but for example, by combining a plurality of rings on a concentric axis, each ring can be independently driven, and the number of types of reagents to be disposed can be increased. Further, the plurality of rings on the concentric axis are different in distance from the center, and the syringe for dispensing the reagent into the cup can be driven by the linear motion with respect to the arrangement position of each measurement unit by utilizing the difference, thereby suppressing the erroneous operation due to the downsizing and the simplification of the driving.

As described above, in any measurement unit, all the cups must be agitated in an intermediate step (for example, after mixing the sample and the reagent). In the apparatus of the present invention, for example, since there is a blood coagulation time measuring means, if the specimen is stirred by a probe (stirring blade), there is a problem such as entanglement of fibrin clot, and therefore the stirring mechanism of the apparatus of the present invention is very effective. Since each cup is independent, the cup structure of the present invention is an important condition for effective stirring of each cup separately. That is, it is possible to stir the mixture with a slight inclination with a wing (a placement projection), and it is advantageous to further include a fixing projection for easy fixing (reliable positioning) in the cup hole. Further, since the shape is a quadrangular prism, the transmission distance of the transmitted light can be precisely fixed, and variations in measurement results can be suppressed.

Therefore, as in the present invention, the cups in the measurement unit including a plurality of different detection systems must be independent of each other, and the cup is preferably in the shape of the present invention in order to enhance the stirring effect.

Conventionally, there is no apparatus configured by integrating 1 apparatus with 3 or more different test systems. Compared with a device formed by connecting different devices of different detection systems, the device has the advantages that the measurement results of a plurality of different detection systems can be obtained in a summary mode 1 time. In the prior art, the measurement results are output by the respective measurement devices.

Industrial applicability

The composite automatic analyzer of the present invention can measure a plurality of kinds of analyses having different measurement accuracies, such as biochemical analysis and immunological analysis, by a single apparatus.

The reaction cuvette of the present invention can be effectively used in an automatic analyzer for performing a stirring operation.

While particular embodiments of the present invention have been described, modifications and improvements will be apparent to those skilled in the art and are intended to be included within the scope of the invention.

Claims

1. A reaction cup characterized in that a concave pit formed by a curved wall surface is provided on the bottom surface of a cup body, an insertion opening for the tip end portion of a stirring rod is provided in the center of the concave pit, and a projection for placement provided so as to project from the upper side surface of the cup body is formed in an arc shape.

2. The cuvette according to claim 1, wherein a fixing projection piece projecting downward from a lower surface of the placement projection is provided on the lower surface.